chr17-82322334-C-A

Variant names:

• chr17-82322334-C-A
• NM_003004.3:c.574G>T

Variant summary

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

The NM_003004.3(SECTM1):​c.574G>T​(p.Ala192Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,294 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: 0.0000014 (0 hom.)
• Consequence: SECTM1 NM_003004.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.53

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=0.03497657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SECTM1	NM_003004.3	c.574G>T	p.Ala192Ser	missense_variant	Exon 5 of 5	ENST00000269389.8	NP_002995.1
SECTM1	XM_005256392.4	c.574G>T	p.Ala192Ser	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.574G>T	p.Ala192Ser	missense_variant	Exon 5 of 5	1	NM_003004.3	ENSP00000269389.3
SECTM1	ENST00000580437	c.*18G>T		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000463904.1
SECTM1	ENST00000581864.5	n.*335G>T		non_coding_transcript_exon_variant	Exon 5 of 5	3		ENSP00000464111.1
SECTM1	ENST00000581864.5	n.*335G>T		3_prime_UTR_variant	Exon 5 of 5	3		ENSP00000464111.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461294 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726934

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.062
DANN	Benign	0.34
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-2.5
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.069
Sift	Benign	0.60	T
Sift4G	Benign	0.69	T
Polyphen		0.0010	B
Vest4		0.050
MutPred		0.33		Loss of helix (P = 0.0033);
MVP		0.055
MPC		0.12
ClinPred		0.027	T
GERP RS		-1.7
Varity_R		0.037
gMVP		0.034

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-80280210; COSMIC: COSV53940878; COSMIC: COSV53940878;