chr6-168059165-G-A

Variant names:

• chr6-168059165-G-A
• rs1548349
• NM_024919.6:c.1366C>T

Variant summary

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

The NM_024919.6(FRMD1):​c.1366C>T​(p.Gln456*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,706 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FRMD1 NM_024919.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 19 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024919.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD1	NM_024919.6	MANE Select	c.1366C>T	p.Gln456*	stop_gained	Exon 10 of 11	NP_079195.3
	FRMD1	NM_001394681.1		c.1171C>T	p.Gln391*	stop_gained	Exon 9 of 10	NP_001381610.1
	FRMD1	NM_001122841.3		c.1162C>T	p.Gln388*	stop_gained	Exon 10 of 11	NP_001116313.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD1	ENST00000283309.11	TSL:1 MANE Select	c.1366C>T	p.Gln456*	stop_gained	Exon 10 of 11	ENSP00000283309.6
	FRMD1	ENST00000432403.5	TSL:1	n.1053C>T		non_coding_transcript_exon	Exon 8 of 9
	FRMD1	ENST00000646385.1		c.1561C>T	p.Gln521*	stop_gained	Exon 13 of 14	ENSP00000494166.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434706 Hom.: 0 Cov.: 51 AF XY: 0.00000141 AC XY: 1 AN XY: 711746

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33262

American (AMR) AF: 0.00 AC: 0 AN: 41898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25744

East Asian (EAS) AF: 0.00 AC: 0 AN: 38840

South Asian (SAS) AF: 0.00 AC: 0 AN: 82632

European-Finnish (FIN) AF: 0.0000221 AC: 1 AN: 45260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5266

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102330

Other (OTH) AF: 0.00 AC: 0 AN: 59474

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Benign	0.90
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.038	N
PhyloP100		-1.1
Vest4		0.021
GERP RS		0.24
Mutation Taster		=111/89	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1548349; hg19: chr6-168459845; COSMIC: COSV51962765; COSMIC: COSV51962765;