8-123774100-A-G

Variant names:

• chr8-123774100-A-G
• rs1341480503
• NM_144963.4:c.93A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_144963.4(FAM91A1):​c.93A>G​(p.Arg31Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,790 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM91A1 NM_144963.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 0 publications found

Genes affected

FAM91A1 (HGNC:26306): (family with sequence similarity 91 member A1) Involved in intracellular protein transport and vesicle tethering to Golgi. Located in cytoplasmic vesicle and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=0.24 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144963.4. 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
	FAM91A1	NM_144963.4	MANE Select	c.93A>G	p.Arg31Arg	synonymous	Exon 2 of 24	NP_659400.3	Q658Y4
	FAM91A1	NM_001317918.1		c.93A>G	p.Arg31Arg	synonymous	Exon 2 of 23	NP_001304847.1	Q658Y4
	FAM91A1	NM_001317917.2		c.-641A>G		5_prime_UTR	Exon 2 of 24	NP_001304846.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM91A1	ENST00000334705.12	TSL:1 MANE Select	c.93A>G	p.Arg31Arg	synonymous	Exon 2 of 24	ENSP00000335082.7	Q658Y4
	FAM91A1	ENST00000519721.5	TSL:1	n.93A>G		non_coding_transcript_exon	Exon 2 of 24	ENSP00000429784.1	G3V120
	FAM91A1	ENST00000913292.1		c.93A>G	p.Arg31Arg	synonymous	Exon 2 of 25	ENSP00000583351.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454790 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723404

African (AFR) AF: 0.00 AC: 0 AN: 33160

American (AMR) AF: 0.00 AC: 0 AN: 43576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39258

South Asian (SAS) AF: 0.00 AC: 0 AN: 84496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5470

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109360

Other (OTH) AF: 0.00 AC: 0 AN: 60082

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.7
DANN	Benign	0.66
PhyloP100		0.24

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: rs1341480503; hg19: chr8-124786340;