rs9940825

Variant names:

• chr16-16198114-C-A
• NM_001171.6:c.1245G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-16198114-C-A
• chr16-16198114-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001171.6(ABCC6):​c.1245G>T​(p.Val415Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,740 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. Synonymous variant affecting the same amino acid position (i.e. V415V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ABCC6 NM_001171.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804

Genes affected

ABCC6 (HGNC:57): (ATP binding cassette subfamily C member 6) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). The encoded protein, a member of the MRP subfamily, is involved in multi-drug resistance. Mutations in this gene cause pseudoxanthoma elasticum. Alternatively spliced transcript variants that encode different proteins have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=0.804 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.1245G>T	p.Val415Val	synonymous_variant	Exon 10 of 31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1	c.903G>T	p.Val301Val	synonymous_variant	Exon 10 of 31		NP_001338729.1
ABCC6	NR_147784.1	n.1282G>T		non_coding_transcript_exon_variant	Exon 10 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.1245G>T	p.Val415Val	synonymous_variant	Exon 10 of 31	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000574094.6	c.1245G>T	p.Val415Val	synonymous_variant	Exon 10 of 11	5		ENSP00000507301.1
ABCC6	ENST00000456970.6	n.1245G>T		non_coding_transcript_exon_variant	Exon 10 of 29	2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.1245G>T		non_coding_transcript_exon_variant	Exon 10 of 32	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459740 Hom.: 0 Cov.: 51 AF XY: 0.00000138 AC XY: 1 AN XY: 725958

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.5
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-16291971;