chr1-182400030-G-T

Position:

• chr1-182400030-G-T

Variant summary

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

The NM_172000.4(TEDDM1):​c.456C>A​(p.Asn152Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: TEDDM1 NM_172000.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0770

Genes affected

TEDDM1 (HGNC:30233): (transmembrane epididymal protein 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.057186782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEDDM1	NM_172000.4	c.456C>A	p.Asn152Lys	missense_variant	1/1	ENST00000367565.2	NP_741997.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEDDM1	ENST00000367565.2	c.456C>A	p.Asn152Lys	missense_variant	1/1	6	NM_172000.4	ENSP00000356536.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Cov.: 73

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74334

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

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

Bravo AF: 0.00000378

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

Nov 17, 2022

The c.456C>A (p.N152K) alteration is located in exon 1 (coding exon 1) of the TEDDM1 gene. This alteration results from a C to A substitution at nucleotide position 456, causing the asparagine (N) at amino acid position 152 to be replaced by a lysine (K). 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	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.3
DANN	Benign	0.72
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.11
Sift	Benign	0.098	T
Sift4G	Benign	0.18	T
Polyphen		0.027	B
Vest4		0.095
MutPred		0.53		Gain of ubiquitination at N152 (P = 0.0311);
MVP		0.048
MPC		0.029
ClinPred		0.026	T
GERP RS		0.66
Varity_R		0.17
gMVP		0.060

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: rs1043935520; hg19: chr1-182369165;