rs117234138

Variant names:

• chr14-24239917-G-A
• rs117234138
• NM_001099274.3:c.1236C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-24239917-G-A
• chr14-24239917-G-C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001099274.3(TINF2):​c.1236C>T​(p.Asn412Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,614,208 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (40 hom.)
• Consequence: TINF2 NM_001099274.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 1.15
• Publications: 1 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: Ambry Genetics, G2P, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Revesz syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, PanelApp Australia
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 14-24239917-G-A is Benign according to our data. Variant chr14-24239917-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 238288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.15 with no splicing effect.
• BS2: High AC in GnomAd4 at 541 AD gene.

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.1236C>T	p.Asn412Asn	synonymous	Exon 9 of 9	NP_001092744.1	Q9BSI4-1
	TINF2	NM_001363668.2		c.1131C>T	p.Asn377Asn	synonymous	Exon 8 of 8	NP_001350597.1	B4DFJ1
	TINF2	NM_012461.3		c.*498C>T		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.1236C>T	p.Asn412Asn	synonymous	Exon 9 of 9	ENSP00000267415.7	Q9BSI4-1
	TINF2	ENST00000399423.8	TSL:1	c.*498C>T		3_prime_UTR	Exon 6 of 6	ENSP00000382350.4	Q9BSI4-2
	TINF2	ENST00000943625.1		c.1182C>T	p.Asn394Asn	synonymous	Exon 9 of 9	ENSP00000613684.1

Frequencies

GnomAD3 genomes AF: 0.00355 AC: 541 AN: 152200 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00541

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00470 AC: 1172 AN: 249564 AF XY: 0.00518

Gnomad AFR exome AF: 0.00110

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.00914

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00482

Gnomad OTH exome AF: 0.00726

GnomAD4 exome AF: 0.00500 AC: 7315 AN: 1461890 Hom.: 40 Cov.: 32 AF XY: 0.00530 AC XY: 3858 AN XY: 727246

African (AFR) AF: 0.000747 AC: 25 AN: 33480

American (AMR) AF: 0.00302 AC: 135 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0103 AC: 270 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0112 AC: 966 AN: 86258

European-Finnish (FIN) AF: 0.00122 AC: 65 AN: 53420

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.00501 AC: 5570 AN: 1112008

Other (OTH) AF: 0.00432 AC: 261 AN: 60396

GnomAD4 genome AF: 0.00355 AC: 541 AN: 152318 Hom.: 4 Cov.: 32 AF XY: 0.00356 AC XY: 265 AN XY: 74470

African (AFR) AF: 0.00120 AC: 50 AN: 41574

American (AMR) AF: 0.00183 AC: 28 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4822

European-Finnish (FIN) AF: 0.000941 AC: 10 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00541 AC: 368 AN: 68024

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00482 Hom.: 1

Bravo AF: 0.00325

Asia WGS AF: 0.00404 AC: 15 AN: 3478

EpiCase AF: 0.00540

EpiControl AF: 0.00409

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	Dyskeratosis congenita (2)
-	-	1	Dyskeratosis congenita, autosomal dominant 3 (1)
-	-	1	not specified (1)
-	-	1	Revesz syndrome (1)
-	-	1	Revesz syndrome;C3151445:Dyskeratosis congenita, autosomal dominant 3;C4551974:Dyskeratosis congenita, autosomal dominant 1 (1)
-	-	1	TINF2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.8
DANN	Benign	0.77
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs117234138; hg19: chr14-24709123;