6-168057250-C-A

Variant names:

• chr6-168057250-C-A
• rs144169920
• NM_024919.6:c.1497G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_024919.6(FRMD1):​c.1497G>T​(p.Ala499Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A499A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FRMD1 NM_024919.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851
• Publications: 1 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=-0.851 with no splicing effect.

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.1497G>T	p.Ala499Ala	synonymous	Exon 11 of 11	NP_079195.3
	FRMD1	NM_001394681.1		c.1302G>T	p.Ala434Ala	synonymous	Exon 10 of 10	NP_001381610.1	A0A2R8Y6M2
	FRMD1	NM_001122841.3		c.1293G>T	p.Ala431Ala	synonymous	Exon 11 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.1497G>T	p.Ala499Ala	synonymous	Exon 11 of 11	ENSP00000283309.6	Q8N878-1
	FRMD1	ENST00000432403.5	TSL:1	n.1184G>T		non_coding_transcript_exon	Exon 9 of 9
	FRMD1	ENST00000646385.1		c.1692G>T	p.Ala564Ala	synonymous	Exon 14 of 14	ENSP00000494166.1	A0A2R8Y4L9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 241404 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458218 Hom.: 0 Cov.: 59 AF XY: 0.00000138 AC XY: 1 AN XY: 725246

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110810

Other (OTH) AF: 0.00 AC: 0 AN: 60196

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.65
DANN	Benign	0.42
PhyloP100		-0.85

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: rs144169920; hg19: chr6-168457930;