chr7-102761321-G-A

Variant names:

• chr7-102761321-G-A
• rs1436404168
• NM_001145268.2:c.703G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145268.2(FAM185A):​c.703G>A​(p.Glu235Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,546,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: FAM185A NM_001145268.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.42
• Publications: 0 publications found

Genes affected

FAM185A (HGNC:22412): (family with sequence similarity 185 member A)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28351575).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145268.2. 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
	FAM185A	NM_001145268.2	MANE Select	c.703G>A	p.Glu235Lys	missense	Exon 4 of 8	NP_001138740.2	Q8N0U4-1
	FAM185A	NM_001350987.2		c.703G>A	p.Glu235Lys	missense	Exon 4 of 7	NP_001337916.2
	FAM185A	NM_001145269.2		c.352G>A	p.Glu118Lys	missense	Exon 3 of 7	NP_001138741.2	Q8N0U4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM185A	ENST00000413034.3	TSL:5 MANE Select	c.703G>A	p.Glu235Lys	missense	Exon 4 of 8	ENSP00000395340.2	Q8N0U4-1
	FAM185A	ENST00000950232.1		c.610G>A	p.Glu204Lys	missense	Exon 3 of 7	ENSP00000620291.1
	FAM185A	ENST00000880455.1		c.571G>A	p.Glu191Lys	missense	Exon 3 of 7	ENSP00000550514.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152122 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000657 AC: 1 AN: 152310 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: 0.0000108 AC: 15 AN: 1394678 Hom.: 0 Cov.: 30 AF XY: 0.00000291 AC XY: 2 AN XY: 687670

African (AFR) AF: 0.00 AC: 0 AN: 31188

American (AMR) AF: 0.00 AC: 0 AN: 34914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25088

East Asian (EAS) AF: 0.00 AC: 0 AN: 35266

South Asian (SAS) AF: 0.0000383 AC: 3 AN: 78268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.0000111 AC: 12 AN: 1076890

Other (OTH) AF: 0.00 AC: 0 AN: 57914

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152122 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74312

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

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000189

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	0.087
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.4
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.13
Sift	Benign	0.18	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.41
MutPred		0.32		Gain of ubiquitination at E235 (P = 0.017)
MVP		0.10
ClinPred		0.81	D
GERP RS		4.2
Varity_R		0.12
gMVP		0.61
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1436404168; hg19: chr7-102401768;