rs10514377

chr5-93680850-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032042.6(FAM172A):c.1109-59721A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 152,262 control chromosomes in the GnomAD database, including 364 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 0.044 (364 hom., cov: 32)
• Consequence: FAM172A NM_032042.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333

Genes affected

FAM172A (HGNC:25365): (ARB2 cotranscriptional regulator A) Predicted to contribute to siRNA binding activity. Predicted to be involved in heterochromatin assembly by small RNA; neural crest cell development; and regulation of alternative mRNA splicing, via spliceosome. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM172A	NM_032042.6	c.1109-59721A>G		intron_variant		ENST00000395965.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM172A	ENST00000395965.8	c.1109-59721A>G		intron_variant		1	NM_032042.6	P1

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6733 AN: 152144 Hom.: 356 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0421

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0443 AC: 6748 AN: 152262 Hom.: 364 Cov.: 32 AF XY: 0.0447 AC XY: 3330 AN XY: 74452

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0375

Gnomad4 FIN AF: 0.0446

Gnomad4 NFE AF: 0.0450

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0541 Hom.: 445

Bravo AF: 0.0530

Asia WGS AF: 0.0240 AC: 83 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.72
Dann	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs10514377; hg19: chr5-93016556;