chr6-115968725-C-G

Variant names:

• chr6-115968725-C-G
• rs143351471
• NM_002031.3:c.481G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002031.3(FRK):​c.481G>C​(p.Val161Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V161I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FRK NM_002031.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.875
• Publications: 1 publications found

Genes affected

FRK (HGNC:3955): (fyn related Src family tyrosine kinase) The protein encoded by this gene belongs to the TYR family of protein kinases. This tyrosine kinase is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. [provided by RefSeq, Jul 2008]

ENSG00000289376 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17392987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRK	NM_002031.3	c.481G>C	p.Val161Leu	missense_variant	Exon 3 of 8	ENST00000606080.2	NP_002022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRK	ENST00000606080.2	c.481G>C	p.Val161Leu	missense_variant	Exon 3 of 8	1	NM_002031.3	ENSP00000476145.1
ENSG00000289376	ENST00000692859.3	n.269-66547G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460554 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726490

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.0000225 AC: 1 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 85854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111476

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.88
PrimateAI	Benign	0.31	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.29
MutPred		0.20		Loss of methylation at K163 (P = 0.0867);
MVP		0.30
MPC		0.18
ClinPred		0.15	T
GERP RS		2.9
Varity_R		0.087
gMVP		0.33
Mutation Taster		=89/11	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: rs143351471; hg19: chr6-116289888;