rs145347617

Variant names:

• chr6-168059132-C-A
• NM_024919.6:c.1399G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-168059132-C-A
• chr6-168059132-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024919.6(FRMD1):​c.1399G>T​(p.Val467Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,423,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. V467M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FRMD1 NM_024919.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.992

Genes affected

FRMD1 (HGNC:21240): (FERM domain containing 1) Predicted to be involved in positive regulation of hippo signaling. Predicted to be located in cytoskeleton. Predicted to be active in cytoplasmic side of apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03423834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD1	NM_024919.6	c.1399G>T	p.Val467Leu	missense_variant	Exon 10 of 11	ENST00000283309.11	NP_079195.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD1	ENST00000283309.11	c.1399G>T	p.Val467Leu	missense_variant	Exon 10 of 11	1	NM_024919.6	ENSP00000283309.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1423002 Hom.: 0 Cov.: 35 AF XY: 0.00000142 AC XY: 1 AN XY: 705214

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000236

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0070
DANN	Benign	0.61
DEOGEN2	Benign	0.00093	.;.;T;.;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.41	T;T;T;T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.034	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;.;N;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.95	.;.;N;N;.
REVEL	Benign	0.020
Sift	Benign	1.0	.;.;T;T;.
Sift4G	Benign	1.0	.;.;T;T;.
Polyphen		0.0, 0.0010	.;.;B;B;.
Vest4		0.040, 0.033
MutPred		0.26		.;.;Gain of helix (P = 0.062);.;.;
MVP		0.12
MPC		0.098
ClinPred		0.086	T
GERP RS		-1.4
Varity_R		0.049
gMVP		0.072

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-168459812;