rs35853112

Variant names:

• chr16-4783221-T-A
• rs35853112
• NM_144605.5:c.726+241A>T

Your query was ambiguous. Multiple possible variants found:

• chr16-4783221-T-A
• chr16-4783221-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144605.5(SEPTIN12):​c.726+241A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEPTIN12 NM_144605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529
• Publications: 0 publications found

Genes affected

SEPTIN12 (HGNC:26348): (septin 12) This gene encodes a guanine-nucleotide binding protein and member of the septin family of cytoskeletal GTPases. Septins play important roles in cytokinesis, exocytosis, embryonic development, and membrane dynamics. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

SEPTIN12 Gene-Disease associations (from GenCC):

• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 10

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000285952 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN12	NM_144605.5	c.726+241A>T		intron_variant	Intron 7 of 9	ENST00000268231.13	NP_653206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN12	ENST00000268231.13	c.726+241A>T		intron_variant	Intron 7 of 9	1	NM_144605.5	ENSP00000268231.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 382076 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 201924

African (AFR) AF: 0.00 AC: 0 AN: 10994

American (AMR) AF: 0.00 AC: 0 AN: 16834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11708

East Asian (EAS) AF: 0.00 AC: 0 AN: 24946

South Asian (SAS) AF: 0.00 AC: 0 AN: 44046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1648

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 227356

Other (OTH) AF: 0.00 AC: 0 AN: 21936

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.3
DANN	Benign	0.92
PhyloP100		-0.53

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: rs35853112; hg19: chr16-4833222;