NM_022063.3:c.651-7C>A

Variant names:

• chr10-118310915-G-T
• rs4751651
• NM_022063.3:c.651-7C>A

Variant summary

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

The NM_022063.3(FAM204A):​c.651-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 1,575,166 control chromosomes in the GnomAD database, including 194,812 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (15312 hom., cov: 31)
  • Exomes 𝑓: 0.50 (179500 hom.)
• Consequence: FAM204A NM_022063.3 splice_region, intron
• Scores: Splicing: ADA: 0.00006456
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

Genes affected

FAM204A (HGNC:25794): (family with sequence similarity 204 member A)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM204A	NM_022063.3	c.651-7C>A		splice_region_variant, intron_variant	Intron 8 of 8	ENST00000369183.9	NP_071346.1
FAM204A	NM_001134672.2	c.651-7C>A		splice_region_variant, intron_variant	Intron 7 of 7		NP_001128144.1
FAM204A	XM_005270024.2	c.672-7C>A		splice_region_variant, intron_variant	Intron 9 of 9		XP_005270081.1
FAM204A	XM_047425619.1	c.651-7C>A		splice_region_variant, intron_variant	Intron 9 of 9		XP_047281575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM204A	ENST00000369183.9	c.651-7C>A		splice_region_variant, intron_variant	Intron 8 of 8	1	NM_022063.3	ENSP00000358183.4

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65619 AN: 151448 Hom.: 15310 Cov.: 31

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.488

GnomAD3 exomes AF: 0.478 AC: 109009 AN: 228222 Hom.: 26887 AF XY: 0.484 AC XY: 59863 AN XY: 123648

Gnomad AFR exome AF: 0.245

Gnomad AMR exome AF: 0.520

Gnomad ASJ exome AF: 0.582

Gnomad EAS exome AF: 0.445

Gnomad SAS exome AF: 0.481

Gnomad FIN exome AF: 0.409

Gnomad NFE exome AF: 0.508

Gnomad OTH exome AF: 0.504

GnomAD4 exome AF: 0.498 AC: 708712 AN: 1423600 Hom.: 179500 Cov.: 28 AF XY: 0.498 AC XY: 353113 AN XY: 708660

Gnomad4 AFR exome AF: 0.239

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.580

Gnomad4 EAS exome AF: 0.424

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.408

Gnomad4 NFE exome AF: 0.511

Gnomad4 OTH exome AF: 0.496

GnomAD4 genome AF: 0.433 AC: 65641 AN: 151566 Hom.: 15312 Cov.: 31 AF XY: 0.433 AC XY: 32075 AN XY: 74044

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.488

Alfa AF: 0.511 Hom.: 23582

Bravo AF: 0.435

Asia WGS AF: 0.431 AC: 1500 AN: 3468

EpiCase AF: 0.531

EpiControl AF: 0.538

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000065
dbscSNV1_RF	Benign	0.020
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

Publications

LitVar

Other links and lift over

dbSNP: rs4751651; hg19: chr10-120070427; COSMIC: COSV64988477; COSMIC: COSV64988477;