chr17-82322172-C-T

Variant names:

• chr17-82322172-C-T
• rs758201047
• NM_003004.3:c.736G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_003004.3(SECTM1):​c.736G>A​(p.Ala246Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: SECTM1 NM_003004.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.92

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.01471737).
• BP6: Variant 17-82322172-C-T is Benign according to our data. Variant chr17-82322172-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2379525.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SECTM1	NM_003004.3	c.736G>A	p.Ala246Thr	missense_variant	Exon 5 of 5	ENST00000269389.8	NP_002995.1
SECTM1	XM_005256392.4	c.736G>A	p.Ala246Thr	missense_variant	Exon 5 of 5		XP_005256449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SECTM1	ENST00000269389.8	c.736G>A	p.Ala246Thr	missense_variant	Exon 5 of 5	1	NM_003004.3	ENSP00000269389.3
SECTM1	ENST00000580437	c.*180G>A		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000463904.1
SECTM1	ENST00000581864.5	n.*497G>A		non_coding_transcript_exon_variant	Exon 5 of 5	3		ENSP00000464111.1
SECTM1	ENST00000581864.5	n.*497G>A		3_prime_UTR_variant	Exon 5 of 5	3		ENSP00000464111.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152114 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000108 AC: 27 AN: 250840 Hom.: 0 AF XY: 0.0000738 AC XY: 10 AN XY: 135578

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000753

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000322 AC: 47 AN: 1461466 Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22 AN XY: 727046

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000649

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152114 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74304

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.0000576 AC: 7

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 30, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.26
DANN	Benign	0.33
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.00092	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.0010
Sift	Benign	0.61	T
Sift4G	Benign	0.67	T
Polyphen		0.0030	B
Vest4		0.016
MutPred		0.12		Gain of phosphorylation at A246 (P = 0.0145);
MVP		0.030
MPC		0.13
ClinPred		0.0066	T
GERP RS		-1.3
Varity_R		0.043
gMVP		0.012

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

Publications

LitVar

Other links and lift over

dbSNP: rs758201047; hg19: chr17-80280048;