chr1-231039976-A-G

Position:

• chr1-231039976-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198552.3(FAM89A):​c.236T>C​(p.Leu79Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 1,222,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: FAM89A NM_198552.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.240

Genes affected

FAM89A (HGNC:25057): (family with sequence similarity 89 member A)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05037996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM89A	NM_198552.3	c.236T>C	p.Leu79Pro	missense_variant	1/2	ENST00000366654.5	NP_940954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM89A	ENST00000366654.5	c.236T>C	p.Leu79Pro	missense_variant	1/2	1	NM_198552.3	ENSP00000355614.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000164 AC: 2 AN: 1222784 Hom.: 0 Cov.: 32 AF XY: 0.00000334 AC XY: 2 AN XY: 598558

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.95e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.4
DANN	Benign	0.68
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.14	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.015
Sift	Benign	0.22	T
Sift4G	Benign	0.25	T
Polyphen		0.0020	B
Vest4		0.084
MutPred		0.29		Gain of glycosylation at L79 (P = 0.0038);
MVP		0.040
MPC		0.46
ClinPred		0.060	T
GERP RS		-4.2
Varity_R		0.056
gMVP		0.31

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-231175722;