chr7-44058969-C-A

Variant names:

• chr7-44058969-C-A
• rs747848126
• NM_001014436.3:c.821C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001014436.3(DBNL):​c.821C>A​(p.Ser274Tyr) variant causes a missense 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S274F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DBNL NM_001014436.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989
• Publications: 0 publications found

Genes affected

DBNL (HGNC:2696): (drebrin like) Enables cadherin binding activity. Predicted to be involved in several processes, including Rac protein signal transduction; nervous system development; and podosome assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2101365).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014436.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBNL	NM_001014436.3	MANE Select	c.821C>A	p.Ser274Tyr	missense	Exon 9 of 13	NP_001014436.1	Q9UJU6-1
	DBNL	NM_001122956.2		c.848C>A	p.Ser283Tyr	missense	Exon 9 of 13	NP_001116428.1	Q9UJU6-3
	DBNL	NM_001362723.2		c.845C>A	p.Ser282Tyr	missense	Exon 9 of 13	NP_001349652.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBNL	ENST00000448521.6	TSL:1 MANE Select	c.821C>A	p.Ser274Tyr	missense	Exon 9 of 13	ENSP00000411701.1	Q9UJU6-1
	DBNL	ENST00000494774.5	TSL:1	c.824C>A	p.Ser275Tyr	missense	Exon 9 of 13	ENSP00000419992.1	Q9UJU6-2
	DBNL	ENST00000497184.5	TSL:1	n.2897C>A		non_coding_transcript_exon	Exon 6 of 10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.99
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.063
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.039	D
Polyphen		0.47	P
Vest4		0.36
MutPred		0.29		Gain of catalytic residue at S274 (P = 0.0222)
MVP		0.71
MPC		0.27
ClinPred		0.94	D
GERP RS		4.6
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.099
gMVP		0.24
Mutation Taster		=82/18	polymorphism

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: rs747848126; hg19: chr7-44098568;