12-5494484-C-T

Variant names:

• chr12-5494484-C-T
• rs35988749
• NM_001102654.2:c.309C>T

Variant summary

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

The NM_001102654.2(NTF3):​c.309C>T​(p.Thr103Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,613,804 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (10 hom.)
• Consequence: NTF3 NM_001102654.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.49
• Publications: 2 publications found

Genes affected

NTF3 (HGNC:8023): (neurotrophin 3) The protein encoded by this gene is a member of the neurotrophin family, that controls survival and differentiation of mammalian neurons. This protein is closely related to both nerve growth factor and brain-derived neurotrophic factor. It may be involved in the maintenance of the adult nervous system, and may affect development of neurons in the embryo when it is expressed in human placenta. NTF3-deficient mice generated by gene targeting display severe movement defects of the limbs. The mature peptide of this protein is identical in all mammals examined including human, pig, rat and mouse. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-5494484-C-T is Benign according to our data. Variant chr12-5494484-C-T is described in ClinVar as [Benign]. Clinvar id is 717685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.
• BS2: High AC in GnomAd4 at 374 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTF3	NM_001102654.2	c.309C>T	p.Thr103Thr	synonymous_variant	Exon 2 of 2	ENST00000423158.4	NP_001096124.1
NTF3	NM_002527.5	c.270C>T	p.Thr90Thr	synonymous_variant	Exon 1 of 1		NP_002518.1
NTF3	XM_011520963.3	c.270C>T	p.Thr90Thr	synonymous_variant	Exon 2 of 2		XP_011519265.1
NTF3	XM_047428901.1	c.270C>T	p.Thr90Thr	synonymous_variant	Exon 2 of 2		XP_047284857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTF3	ENST00000423158.4	c.309C>T	p.Thr103Thr	synonymous_variant	Exon 2 of 2	1	NM_001102654.2	ENSP00000397297.2
NTF3	ENST00000331010.7	c.270C>T	p.Thr90Thr	synonymous_variant	Exon 1 of 1	6		ENSP00000328738.6
NTF3	ENST00000543548.1	n.499C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
NTF3	ENST00000535299.5	n.232-12081C>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.00246 AC: 374 AN: 152130 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00415

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.00205 AC: 514 AN: 250742 AF XY: 0.00204

Gnomad AFR exome AF: 0.000678

Gnomad AMR exome AF: 0.000925

Gnomad ASJ exome AF: 0.00566

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000471

Gnomad NFE exome AF: 0.00345

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00353 AC: 5163 AN: 1461556 Hom.: 10 Cov.: 36 AF XY: 0.00342 AC XY: 2486 AN XY: 727080

African (AFR) AF: 0.000568 AC: 19 AN: 33480

American (AMR) AF: 0.000827 AC: 37 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00478 AC: 125 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.000735 AC: 39 AN: 53086

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00430 AC: 4780 AN: 1112008

Other (OTH) AF: 0.00267 AC: 161 AN: 60396

GnomAD4 genome AF: 0.00246 AC: 374 AN: 152248 Hom.: 1 Cov.: 32 AF XY: 0.00211 AC XY: 157 AN XY: 74438

African (AFR) AF: 0.000698 AC: 29 AN: 41556

American (AMR) AF: 0.00150 AC: 23 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00415 AC: 282 AN: 68024

Other (OTH) AF: 0.00285 AC: 6 AN: 2108

Alfa AF: 0.00367 Hom.: 0

Bravo AF: 0.00214

EpiCase AF: 0.00311

EpiControl AF: 0.00314

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 14, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.12
DANN	Benign	0.71
PhyloP100		-1.5
PromoterAI		-0.0012	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs35988749; hg19: chr12-5603650; COSMIC: COSV58417356;