Genetic Variant SECTM1:p.Gln175* (chr17-82322892-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003004.3(SECTM1):c.523C>T(p.Gln175*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,613,768 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 5 hom. )

Consequence

SECTM1
NM_003004.3 stop_gained

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.79

Variant links:

Genes affected

SECTM1 (HGNC:10707): (secreted and transmembrane 1) This gene encodes a transmembrane and secreted protein with characteristics of a type 1a transmembrane protein. It is found in a perinuclear Golgi-like pattern and thought to be involved in hematopoietic and/or immune system processes. [provided by RefSeq, Jul 2008]

SECTM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SECTM1	NM_003004.3 link	c.523C>T	p.Gln175*	stop_gained	Exon 4 of 5	ENST00000269389.8	NP_002995.1	Q8WVN6
SECTM1	XM_005256392.4 link	c.523C>T	p.Gln175*	stop_gained	Exon 4 of 5		XP_005256449.1	Q8WVN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SECTM1	ENST00000269389.8 link	c.523C>T	p.Gln175*	stop_gained	Exon 4 of 5	1	NM_003004.3	ENSP00000269389.3		Q8WVN6

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

173

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000556

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00134

AC:

336

AN:

250290

Hom.:

AF XY:

0.00128

AC XY:

173

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.000557

Gnomad AMR exome

AF:

0.000782

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000686

Gnomad FIN exome

AF:

0.000417

Gnomad NFE exome

AF:

0.00221

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00174

AC:

2550

AN:

1461494

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

1254

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000719

Gnomad4 FIN exome

AF:

0.000339

Gnomad4 NFE exome

AF:

0.00205

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00114

AC:

173

AN:

152274

Hom.:

Cov.:

AF XY:

0.000900

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00206

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00180

Hom.:

Bravo

AF:

0.00120

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00143

AC:

174

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Oct 16, 2019

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Benign

0.86

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.0051

Vest4

0.077

GERP RS

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over