17-7041768-G-T

Variant names:

• chr17-7041768-G-T
• rs75493593
• NM_001370549.1:c.1255C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370549.1(SLC16A11):​c.1255C>A​(p.Pro419Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,613,562 control chromosomes in the GnomAD database, including 2,566 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.025 (269 hom., cov: 32)
  • Exomes 𝑓: 0.018 (2297 hom.)
• Consequence: SLC16A11 NM_001370549.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 46 publications found

Genes affected

SLC16A11 (HGNC:23093): (solute carrier family 16 member 11) Enables pyruvate transmembrane transporter activity. Involved in lipid metabolic process. Located in endoplasmic reticulum membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015069842).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370549.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A11	NM_001370549.1	MANE Select	c.1255C>A	p.Pro419Thr	missense	Exon 5 of 5	NP_001357478.1
	SLC16A11	NM_153357.3		c.1255C>A	p.Pro419Thr	missense	Exon 4 of 4	NP_699188.2
	SLC16A11	NM_001370553.1		c.*163C>A		3_prime_UTR	Exon 4 of 4	NP_001357482.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A11	ENST00000574600.3	TSL:3 MANE Select	c.1255C>A	p.Pro419Thr	missense	Exon 5 of 5	ENSP00000460927.2
	SLC16A11	ENST00000573338.1	TSL:1	n.818C>A		non_coding_transcript_exon	Exon 2 of 2
	SLC16A11	ENST00000662352.3		c.1255C>A	p.Pro419Thr	missense	Exon 4 of 4	ENSP00000499634.1

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3814 AN: 152054 Hom.: 269 Cov.: 32

Gnomad AFR AF: 0.00476

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.0967

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00704

Gnomad OTH AF: 0.0311

GnomAD2 exomes AF: 0.0543 AC: 13523 AN: 248848 AF XY: 0.0430

Gnomad AFR exome AF: 0.00499

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.00941

Gnomad EAS exome AF: 0.0974

Gnomad FIN exome AF: 0.0208

Gnomad NFE exome AF: 0.00600

Gnomad OTH exome AF: 0.0402

GnomAD4 exome AF: 0.0180 AC: 26265 AN: 1461390 Hom.: 2297 Cov.: 32 AF XY: 0.0164 AC XY: 11913 AN XY: 726984

African (AFR) AF: 0.00311 AC: 104 AN: 33478

American (AMR) AF: 0.280 AC: 12504 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00911 AC: 238 AN: 26128

East Asian (EAS) AF: 0.0906 AC: 3597 AN: 39696

South Asian (SAS) AF: 0.00445 AC: 384 AN: 86250

European-Finnish (FIN) AF: 0.0186 AC: 987 AN: 53158

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5688

European-Non Finnish (NFE) AF: 0.00661 AC: 7349 AN: 1111960

Other (OTH) AF: 0.0182 AC: 1096 AN: 60378

GnomAD4 genome AF: 0.0251 AC: 3817 AN: 152172 Hom.: 269 Cov.: 32 AF XY: 0.0280 AC XY: 2082 AN XY: 74396

African (AFR) AF: 0.00474 AC: 197 AN: 41524

American (AMR) AF: 0.150 AC: 2290 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.0964 AC: 497 AN: 5158

South Asian (SAS) AF: 0.00767 AC: 37 AN: 4822

European-Finnish (FIN) AF: 0.0213 AC: 226 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00705 AC: 479 AN: 67988

Other (OTH) AF: 0.0303 AC: 64 AN: 2114

Alfa AF: 0.00611 Hom.: 10

Bravo AF: 0.0383

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00986 AC: 38

ESP6500AA AF: 0.00386 AC: 17

ESP6500EA AF: 0.00746 AC: 64

ExAC AF: 0.0432 AC: 5241

Asia WGS AF: 0.0460 AC: 160 AN: 3478

EpiCase AF: 0.00682

EpiControl AF: 0.00622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0060	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.1
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.052
Sift	Benign	0.31	T
Sift4G	Uncertain	0.036	D
Polyphen		0.89	P
Vest4		0.23
MPC		1.1
ClinPred		0.017	T
GERP RS		5.1
Varity_R		0.087
gMVP		0.42
Mutation Taster		=94/6	polymorphism (auto)

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: rs75493593; hg19: chr17-6945087; COSMIC: COSV57274354; COSMIC: COSV57274354;