6-70561176-C-A

Variant names:

• chr6-70561176-C-A
• rs9455158
• ENST00000856122.1:c.*1255C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000856122.1(FAM135A):​c.*1255C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,872 control chromosomes in the GnomAD database, including 6,824 homozygotes. 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: 𝑓 0.27 (6822 hom., cov: 33)
  • Exomes 𝑓: 0.18 (2 hom.)
• Consequence: FAM135A ENST00000856122.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 3 publications found

Genes affected

FAM135A (HGNC:21084): (family with sequence similarity 135 member A) Predicted to be involved in cellular lipid metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000856122.1. 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
	FAM135A	NM_001162529.3	MANE Select	c.*1255C>A		downstream_gene	N/A	NP_001156001.1	Q9P2D6-1
	FAM135A	NM_001330996.3		c.*1255C>A		downstream_gene	N/A	NP_001317925.1
	FAM135A	NM_001330999.3		c.*1255C>A		downstream_gene	N/A	NP_001317928.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM135A	ENST00000856122.1		c.*1255C>A		3_prime_UTR	Exon 23 of 23	ENSP00000526181.1
	FAM135A	ENST00000935394.1		c.*1255C>A		3_prime_UTR	Exon 23 of 23	ENSP00000605453.1
	FAM135A	ENST00000935395.1		c.*1255C>A		3_prime_UTR	Exon 22 of 22	ENSP00000605454.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40235 AN: 151638 Hom.: 6785 Cov.: 33

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.0650

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0945

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.253

GnomAD4 exome AF: 0.178 AC: 21 AN: 118 Hom.: 2 Cov.: 0 AF XY: 0.125 AC XY: 9 AN XY: 72

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.181 AC: 21 AN: 116

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.266 AC: 40326 AN: 151754 Hom.: 6822 Cov.: 33 AF XY: 0.265 AC XY: 19615 AN XY: 74134

African (AFR) AF: 0.478 AC: 19765 AN: 41384

American (AMR) AF: 0.219 AC: 3343 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3468

East Asian (EAS) AF: 0.0941 AC: 487 AN: 5174

South Asian (SAS) AF: 0.161 AC: 774 AN: 4808

European-Finnish (FIN) AF: 0.245 AC: 2566 AN: 10492

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12330 AN: 67874

Other (OTH) AF: 0.256 AC: 540 AN: 2108

Alfa AF: 0.245 Hom.: 840

Bravo AF: 0.271

Asia WGS AF: 0.208 AC: 723 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.7
DANN	Benign	0.67
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9455158; hg19: chr6-71270879;