chr6-168060836-C-T

Variant names:

• chr6-168060836-C-T
• rs148097635
• NM_024919.6:c.1267G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024919.6(FRMD1):​c.1267G>A​(p.Gly423Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,613,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: FRMD1 NM_024919.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011752754).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD1	NM_024919.6	MANE Select	c.1267G>A	p.Gly423Arg	missense	Exon 9 of 11	NP_079195.3
	FRMD1	NM_001394681.1		c.1072G>A	p.Gly358Arg	missense	Exon 8 of 10	NP_001381610.1	A0A2R8Y6M2
	FRMD1	NM_001122841.3		c.1063G>A	p.Gly355Arg	missense	Exon 9 of 11	NP_001116313.1	Q8N878-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD1	ENST00000283309.11	TSL:1 MANE Select	c.1267G>A	p.Gly423Arg	missense	Exon 9 of 11	ENSP00000283309.6	Q8N878-1
	FRMD1	ENST00000432403.5	TSL:1	n.954G>A		non_coding_transcript_exon	Exon 7 of 9
	FRMD1	ENST00000646385.1		c.1462G>A	p.Gly488Arg	missense	Exon 12 of 14	ENSP00000494166.1	A0A2R8Y4L9

Frequencies

GnomAD3 genomes AF: 0.000624 AC: 95 AN: 152206 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.000563 AC: 141 AN: 250324 AF XY: 0.000575

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.000579

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.000762

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000876

Gnomad OTH exome AF: 0.000655

GnomAD4 exome AF: 0.00112 AC: 1635 AN: 1461244 Hom.: 0 Cov.: 32 AF XY: 0.00106 AC XY: 767 AN XY: 726964

African (AFR) AF: 0.000149 AC: 5 AN: 33478

American (AMR) AF: 0.000581 AC: 26 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26132

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.0000757 AC: 4 AN: 52868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00137 AC: 1523 AN: 1111950

Other (OTH) AF: 0.00101 AC: 61 AN: 60388

GnomAD4 genome AF: 0.000630 AC: 96 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.000497 AC XY: 37 AN XY: 74476

African (AFR) AF: 0.000168 AC: 7 AN: 41580

American (AMR) AF: 0.000588 AC: 9 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00109 AC: 74 AN: 68028

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.00104 Hom.: 0

Bravo AF: 0.000703

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00198 AC: 17

ExAC AF: 0.000503 AC: 61

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000889

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.9
DANN	Benign	0.78
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.2
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.016
Sift	Benign	0.62	T
Sift4G	Benign	0.58	T
Polyphen		0.57	P
Vest4		0.074
MutPred		0.24		Gain of solvent accessibility (P = 0.0471)
MVP		0.38
MPC		0.13
ClinPred		0.0043	T
GERP RS		-2.6
Varity_R		0.036
gMVP		0.11
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs148097635; hg19: chr6-168461516;