17-82322333-G-C

Position:

• chr17-82322333-G-C

Variant summary

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

The NM_003004.3(SECTM1):​c.575C>G​(p.Ala192Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,416 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: SECTM1 NM_003004.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.01

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048036367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SECTM1	NM_003004.3	c.575C>G	p.Ala192Gly	missense_variant	5/5	ENST00000269389.8	NP_002995.1
SECTM1	XM_005256392.4	c.575C>G	p.Ala192Gly	missense_variant	5/5		XP_005256449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SECTM1	ENST00000269389.8	c.575C>G	p.Ala192Gly	missense_variant	5/5	1	NM_003004.3	ENSP00000269389.3
SECTM1	ENST00000580437.5	c.*19C>G		3_prime_UTR_variant	5/5	2		ENSP00000463904.1
SECTM1	ENST00000581864.5	n.*336C>G		non_coding_transcript_exon_variant	5/5	3		ENSP00000464111.1
SECTM1	ENST00000581864.5	n.*336C>G		3_prime_UTR_variant	5/5	3		ENSP00000464111.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1461416 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727006

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2024

The c.575C>G (p.A192G) alteration is located in exon 5 (coding exon 4) of the SECTM1 gene. This alteration results from a C to G substitution at nucleotide position 575, causing the alanine (A) at amino acid position 192 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.95
DANN	Benign	0.39
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.00061	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.0
Sift	Benign	0.51	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.26		Loss of helix (P = 0.0104);
MVP		0.067
MPC		0.14
ClinPred		0.025	T
GERP RS		-1.7
Varity_R		0.028
gMVP		0.027

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-80280209;