NM_001171.6:c.2631C>T

Variant names:

• chr16-16175946-G-A
• rs72664285
• NM_001171.6:c.2631C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001171.6(ABCC6):​c.2631C>T​(p.Thr877Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T877T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCC6 NM_001171.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.217

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26068708).
• BP6: Variant 16-16175946-G-A is Benign according to our data. Variant chr16-16175946-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2770830.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.217 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.2631C>T	p.Thr877Thr	synonymous_variant	Exon 20 of 31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1	c.2289C>T	p.Thr763Thr	synonymous_variant	Exon 20 of 31		NP_001338729.1
ABCC6	NR_147784.1	n.2493C>T		non_coding_transcript_exon_variant	Exon 19 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.2631C>T	p.Thr877Thr	synonymous_variant	Exon 20 of 31	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000456970.6	n.2456C>T		non_coding_transcript_exon_variant	Exon 19 of 29	2		ENSP00000405002.2
ABCC6	ENST00000576683.1	n.118C>T		non_coding_transcript_exon_variant	Exon 2 of 3	3
ABCC6	ENST00000622290.5	n.2631C>T		non_coding_transcript_exon_variant	Exon 20 of 32	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 28, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.58
DANN	Benign	0.25
Eigen	Benign	-0.78
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.53	T
Sift4G	Benign	0.95	T
Vest4		0.20
MutPred		0.37		Loss of sheet (P = 3e-04);
MVP		0.14
ClinPred		0.025	T
GERP RS		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs72664285; hg19: chr16-16269803;