6-168062944-G-A

Variant names:

• chr6-168062944-G-A
• rs902393
• NM_024919.6:c.820C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024919.6(FRMD1):​c.820C>T​(p.Arg274Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 1,611,900 control chromosomes in the GnomAD database, including 4,418 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.071 (389 hom., cov: 34)
  • Exomes 𝑓: 0.074 (4029 hom.)
• Consequence: FRMD1 NM_024919.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 15 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032986403).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0746 is higher than 0.05.

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.820C>T	p.Arg274Cys	missense	Exon 7 of 11	NP_079195.3
	FRMD1	NM_001394681.1		c.556C>T	p.Arg186Cys	missense	Exon 5 of 10	NP_001381610.1
	FRMD1	NM_001122841.3		c.616C>T	p.Arg206Cys	missense	Exon 7 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.820C>T	p.Arg274Cys	missense	Exon 7 of 11	ENSP00000283309.6
	FRMD1	ENST00000432403.5	TSL:1	n.438C>T		non_coding_transcript_exon	Exon 4 of 9
	FRMD1	ENST00000646385.1		c.946C>T	p.Arg316Cys	missense	Exon 9 of 14	ENSP00000494166.1

Frequencies

GnomAD3 genomes AF: 0.0709 AC: 10788 AN: 152098 Hom.: 390 Cov.: 34

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.0499

Gnomad SAS AF: 0.0771

Gnomad FIN AF: 0.0861

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0763

Gnomad OTH AF: 0.0612

GnomAD2 exomes AF: 0.0707 AC: 17780 AN: 251398 AF XY: 0.0717

Gnomad AFR exome AF: 0.0701

Gnomad AMR exome AF: 0.0502

Gnomad ASJ exome AF: 0.0698

Gnomad EAS exome AF: 0.0550

Gnomad FIN exome AF: 0.0852

Gnomad NFE exome AF: 0.0742

Gnomad OTH exome AF: 0.0645

GnomAD4 exome AF: 0.0739 AC: 107922 AN: 1459684 Hom.: 4029 Cov.: 32 AF XY: 0.0741 AC XY: 53817 AN XY: 726292

African (AFR) AF: 0.0651 AC: 2179 AN: 33450

American (AMR) AF: 0.0517 AC: 2311 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 1889 AN: 26126

East Asian (EAS) AF: 0.0518 AC: 2055 AN: 39698

South Asian (SAS) AF: 0.0790 AC: 6814 AN: 86246

European-Finnish (FIN) AF: 0.0887 AC: 4733 AN: 53376

Middle Eastern (MID) AF: 0.0350 AC: 202 AN: 5764

European-Non Finnish (NFE) AF: 0.0753 AC: 83567 AN: 1110000

Other (OTH) AF: 0.0692 AC: 4172 AN: 60314

GnomAD4 genome AF: 0.0710 AC: 10804 AN: 152216 Hom.: 389 Cov.: 34 AF XY: 0.0706 AC XY: 5252 AN XY: 74414

African (AFR) AF: 0.0696 AC: 2891 AN: 41524

American (AMR) AF: 0.0530 AC: 811 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3472

East Asian (EAS) AF: 0.0502 AC: 260 AN: 5176

South Asian (SAS) AF: 0.0775 AC: 374 AN: 4824

European-Finnish (FIN) AF: 0.0861 AC: 913 AN: 10604

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0763 AC: 5189 AN: 68004

Other (OTH) AF: 0.0610 AC: 129 AN: 2114

Alfa AF: 0.0728 Hom.: 2020

Bravo AF: 0.0684

TwinsUK AF: 0.0752 AC: 279

ALSPAC AF: 0.0760 AC: 293

ESP6500AA AF: 0.0670 AC: 295

ESP6500EA AF: 0.0719 AC: 618

ExAC AF: 0.0725 AC: 8807

Asia WGS AF: 0.0620 AC: 217 AN: 3478

EpiCase AF: 0.0682

EpiControl AF: 0.0680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	3.5
DANN	Benign	0.79
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.84	L
PhyloP100		-0.072
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.081
Sift	Benign	0.061	T
Sift4G	Benign	0.082	T
Polyphen		0.0040	B
Vest4		0.086
MPC		0.14
ClinPred		0.0072	T
GERP RS		-1.9
Varity_R		0.10
gMVP		0.23
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs902393; hg19: chr6-168463624; COSMIC: COSV51961481; COSMIC: COSV51961481;