rs376517606

Variant names:

• chr2-27663922-A-G
• rs376517606
• NM_018158.3:c.8A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-27663922-A-G
• chr2-27663922-A-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018158.3(SLC4A1AP):​c.8A>G​(p.Asp3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: SLC4A1AP NM_018158.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.917
• Publications: 0 publications found

Genes affected

SLC4A1AP (HGNC:13813): (solute carrier family 4 member 1 adaptor protein) Predicted to enable mRNA binding activity. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SUPT7L (HGNC:30632): (SPT7 like, STAGA complex subunit gamma) SUPT7L is a protein subunit of the human STAGA complex (SPT3; (MIM 602947)/TAF9 (MIM 600822)/GCN5 (MIM 602301) acetyltransferase complex), which is a chromatin-modifying multiprotein complex (Martinez et al., 2001 [PubMed 11564863]).[supplied by OMIM, Apr 2009]

SUPT7L Gene-Disease associations (from GenCC):

• lipodystrophy

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04780817).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018158.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A1AP	NM_018158.3	MANE Select	c.8A>G	p.Asp3Gly	missense	Exon 1 of 14	NP_060628.3	Q9BWU0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A1AP	ENST00000326019.11	TSL:1 MANE Select	c.8A>G	p.Asp3Gly	missense	Exon 1 of 14	ENSP00000323837.7	Q9BWU0-2
	SLC4A1AP	ENST00000618046.4	TSL:1	c.8A>G	p.Asp3Gly	missense	Exon 1 of 14	ENSP00000483501.1	Q9BWU0-2
	SLC4A1AP	ENST00000901631.1		c.8A>G	p.Asp3Gly	missense	Exon 1 of 14	ENSP00000571690.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152150 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000597 AC: 15 AN: 251460 AF XY: 0.0000441

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461894 Hom.: 0 Cov.: 29 AF XY: 0.0000220 AC XY: 16 AN XY: 727248

African (AFR) AF: 0.000388 AC: 13 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112012

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152150 Hom.: 0 Cov.: 31 AF XY: 0.0000942 AC XY: 7 AN XY: 74318

African (AFR) AF: 0.000338 AC: 14 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000197 Hom.: 0

Bravo AF: 0.000113

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.92
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.041
Sift	Uncertain	0.026	D
Sift4G	Benign	0.065	T
Polyphen		0.99	D
Vest4		0.21
MVP		0.36
MPC		0.35
ClinPred		0.10	T
GERP RS		0.19
PromoterAI		-0.068	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.24
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs376517606; hg19: chr2-27886789;