chr16-260381-G-C

Variant names:

• chr16-260381-G-C
• rs13335629
• NM_032039.4:c.577+221G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032039.4(FAM234A):​c.577+221G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000226 in 441,606 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: 0.0000023 (0 hom.)
• Consequence: FAM234A NM_032039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• Publications: 9 publications found

Genes affected

FAM234A (HGNC:14163): (family with sequence similarity 234 member A) Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032039.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM234A	NM_032039.4	MANE Select	c.577+221G>C		intron	N/A	NP_114428.1
	FAM234A	NM_001284497.2		c.577+221G>C		intron	N/A	NP_001271426.1
	FAM234A	NR_104317.2		n.753+221G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM234A	ENST00000399932.8	TSL:1 MANE Select	c.577+221G>C		intron	N/A	ENSP00000382814.3
	FAM234A	ENST00000301678.7	TSL:1	c.577+221G>C		intron	N/A	ENSP00000301678.3
	FAM234A	ENST00000301679.7	TSL:2	c.577+221G>C		intron	N/A	ENSP00000301679.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000226 AC: 1 AN: 441606 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 233080

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

African (AFR) AF: 0.00 AC: 0 AN: 12584

American (AMR) AF: 0.00 AC: 0 AN: 20890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13530

East Asian (EAS) AF: 0.00 AC: 0 AN: 29634

South Asian (SAS) AF: 0.00 AC: 0 AN: 47670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3438

European-Non Finnish (NFE) AF: 0.00000385 AC: 1 AN: 259450

Other (OTH) AF: 0.00 AC: 0 AN: 25204

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 203

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs13335629; hg19: chr16-310380;