chr7-102749422-G-T

Variant names:

• chr7-102749422-G-T
• rs1405304722
• NM_001145268.2:c.215G>T

Variant summary

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

The NM_001145268.2(FAM185A):​c.215G>T​(p.Ser72Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,094 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S72T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: FAM185A NM_001145268.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• 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=0.337878).

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.215G>T	p.Ser72Ile	missense	Exon 1 of 8	NP_001138740.2	Q8N0U4-1
	FAM185A	NM_001350987.2		c.215G>T	p.Ser72Ile	missense	Exon 1 of 7	NP_001337916.2
	FAM185A	NM_001145269.2		c.210+5G>T		splice_region intron	N/A	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.215G>T	p.Ser72Ile	missense	Exon 1 of 8	ENSP00000395340.2	Q8N0U4-1
	FAM185A	ENST00000950232.1		c.215G>T	p.Ser72Ile	missense	Exon 1 of 7	ENSP00000620291.1
	FAM185A	ENST00000880455.1		c.215G>T	p.Ser72Ile	missense	Exon 1 of 7	ENSP00000550514.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396094 Hom.: 0 Cov.: 35 AF XY: 0.00000145 AC XY: 1 AN XY: 688540

African (AFR) AF: 0.00 AC: 0 AN: 31506

American (AMR) AF: 0.00 AC: 0 AN: 35656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25144

East Asian (EAS) AF: 0.00 AC: 0 AN: 35718

South Asian (SAS) AF: 0.00 AC: 0 AN: 79102

European-Finnish (FIN) AF: 0.0000206 AC: 1 AN: 48546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078394

Other (OTH) AF: 0.00 AC: 0 AN: 57792

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.10
Eigen_PC	Benign	-0.0099
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.7
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.26
Sift	Benign	0.15	T
Sift4G	Benign	0.29	T
Polyphen		1.0	D
Vest4		0.41
MutPred		0.42		Loss of disorder (P = 0.0163)
MVP		0.14
ClinPred		0.99	D
GERP RS		1.2
PromoterAI		-0.083	Neutral
Varity_R		0.36
gMVP		0.70
Mutation Taster		=71/29	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: rs1405304722; hg19: chr7-102389869;