rs10141326

Variant names:

• chr14-24240145-C-T
• rs10141326
• NM_001099274.3:c.1140G>A
• TINF2 p.Pro380Pro

Your query was ambiguous. Multiple possible variants found:

• chr14-24240145-C-T
• chr14-24240145-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001099274.3(TINF2):​c.1140G>A​(p.Pro380Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,613,890 control chromosomes in the GnomAD database, including 1,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (863 hom., cov: 32)
  • Exomes 𝑓: 0.0062 (780 hom.)
• Consequence: TINF2 NM_001099274.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.183
• Publications: 5 publications found

Genes affected

TINF2 (HGNC:11824): (TERF1 interacting nuclear factor 2) This gene encodes one of the proteins of the shelterin, or telosome, complex which protects telomeres by allowing the cell to distinguish between telomeres and regions of DNA damage. The protein encoded by this gene is a critical part of shelterin; it interacts with the three DNA-binding proteins of the shelterin complex, and it is important for assembly of the complex. Mutations in this gene cause dyskeratosis congenita (DKC), an inherited bone marrow failure syndrome. [provided by RefSeq, Mar 2010]

TINF2 Gene-Disease associations (from GenCC):

• dyskeratosis congenita, autosomal dominant 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, ClinGen, Ambry Genetics
• Revesz syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet
• pulmonary fibrosis

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• dyskeratosis congenita

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Hoyeraal-Hreidarsson syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• thyroid gland papillary carcinoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 14-24240145-C-T is Benign according to our data. Variant chr14-24240145-C-T is described in ClinVar as Benign. ClinVar VariationId is 312946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.183 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099274.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TINF2	NM_001099274.3	MANE Select	c.1140G>A	p.Pro380Pro	synonymous	Exon 8 of 9	NP_001092744.1	Q9BSI4-1
	TINF2	NM_001363668.2		c.1035G>A	p.Pro345Pro	synonymous	Exon 7 of 8	NP_001350597.1	B4DFJ1
	TINF2	NM_012461.3		c.*270G>A		3_prime_UTR	Exon 6 of 6	NP_036593.2	Q9BSI4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TINF2	ENST00000267415.12	TSL:1 MANE Select	c.1140G>A	p.Pro380Pro	synonymous	Exon 8 of 9	ENSP00000267415.7	Q9BSI4-1
	TINF2	ENST00000399423.8	TSL:1	c.*270G>A		3_prime_UTR	Exon 6 of 6	ENSP00000382350.4	Q9BSI4-2
	TINF2	ENST00000943625.1		c.1086G>A	p.Pro362Pro	synonymous	Exon 8 of 9	ENSP00000613684.1

Frequencies

GnomAD3 genomes AF: 0.0589 AC: 8944 AN: 151886 Hom.: 858 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.000867

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.0459

GnomAD2 exomes AF: 0.0150 AC: 3737 AN: 249562 AF XY: 0.0112

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.0118

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000856

Gnomad OTH exome AF: 0.00874

GnomAD4 exome AF: 0.00621 AC: 9076 AN: 1461886 Hom.: 780 Cov.: 32 AF XY: 0.00535 AC XY: 3894 AN XY: 727242

African (AFR) AF: 0.208 AC: 6957 AN: 33478

American (AMR) AF: 0.0128 AC: 573 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 27 AN: 26136

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39700

South Asian (SAS) AF: 0.000522 AC: 45 AN: 86258

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53414

Middle Eastern (MID) AF: 0.0139 AC: 80 AN: 5768

European-Non Finnish (NFE) AF: 0.000460 AC: 512 AN: 1112012

Other (OTH) AF: 0.0144 AC: 871 AN: 60396

GnomAD4 genome AF: 0.0590 AC: 8970 AN: 152004 Hom.: 863 Cov.: 32 AF XY: 0.0576 AC XY: 4277 AN XY: 74286

African (AFR) AF: 0.202 AC: 8371 AN: 41418

American (AMR) AF: 0.0268 AC: 409 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.000867 AC: 3 AN: 3462

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4800

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10592

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00112 AC: 76 AN: 67990

Other (OTH) AF: 0.0454 AC: 96 AN: 2114

Alfa AF: 0.0319 Hom.: 305

Bravo AF: 0.0668

Asia WGS AF: 0.0250 AC: 86 AN: 3478

EpiCase AF: 0.00136

EpiControl AF: 0.00101

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Dyskeratosis congenita (1)
-	-	1	Dyskeratosis congenita, autosomal dominant 3 (1)
-	-	1	Revesz syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.6
DANN	Benign	0.65
PhyloP100		0.18
PromoterAI		0.0020	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10141326;

hg19: chr14-24709351;